Hypercalcemia can occur as a result of numerous different clinical conditions, wherein there are produced high concentrations of free calcium ions in the circulating blood. Causes of hypercalcemia can include for example, hyperparathyroidism, cancer (with or without bone metastasis), hypervitaminosis D, sarcoidosis, thyrotoxicosis, immobility and adrenal insufficiency, among others.
Present treatments for hypercalcemia include vigorous intravenous hydration with diuresis to purge calcium from a patient's body. Furthermore, glucocorticoids are also occasionally used in conjunction with such intravenous hydration techniques to lower serum calcium levels. Other methods, which have been utilized to treat hypercalcemia, include administering Mitomycin (a chemotherapeutic agent directly toxic to tumor cells and which can decrease plasma calcium levels), administering calcitonin (a thyroid hormone which can inhibit bone resorption and thus decrease plasma calcium levels), Etidronate (a chemical compound which binds to calcium phosphate surfaces and inhibits crystal resorption of bone) and administering phosphate. Treatment results with each of the above discussed methods are relatively short lived, and as a consequence, hypercalcemia often readily returns after each of the above discussed treatments are discontinued.
Suramin was used by Stein et al in clinical trials to treat patients with adrenalcortical carcinoma, renal cell carcinoma and leukemia/lymphoma (J. of Clinical Oncology, Vol. 7, pp. 499-508, 1989). Stein et al reported that they treated a patient with cancer metastatic to bone and with hypercalcemia refractory to calcitonin. The patients' hypercalcemia normalized for three months after initiation of suramin therapy in the setting of disease stabilization radiographically. J. of Clinical Oncology, Vol. 7, pp. 499-508 (1989) is incorporated herein by reference.
Stein et al, in U.S. patent application, Ser. No. 07/321,055, filed on Mar. 9, 1989, disclose a general method for treating cancer in a patient by administering suramin sodium to a patient so that suramin serum (plasma) levels are maintained between about 50-300 mcg/ml. U.S. patent application Ser. No. 07/321,055 of Stein et al is incorporated herein by reference.
Jentsch et al in J. Gen. Virol., Vol. 68, pp. 2183-2192 (1987) tested 90 analogues of suramin for their ability to inhibit the exogenous reverse transcriptase (RT) of human immuno-deficiency virus type I (HIV-I). Of the compounds tested, 57 suramin analogues inhibited poly (rC)oligo (dG) dependent RT activity. The Jentsch et al reference is incorporated herein by reference, as are the structures of the 90 suramin analogues disclosed therein.